dbSNP rs587776902: SCARF2:p.Val443AspfsTer78 (chr22-20429630-TCA-T) – ACMG Classification: Pathogenic (12 pts)

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_182895.5(SCARF2):c.1328_1329delTG(p.Val443AspfsTer78) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCARF2
NM_182895.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 3.92

Variant links:

Genes affected

SCARF2 (HGNC:19869): (scavenger receptor class F member 2) The protein encoded by this gene is similar to SCARF1/SREC-I, a scavenger receptor protein that mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). This protein has only little activity of internalizing modified low density lipoproteins (LDL), but it can interact with SCARF1 through its extracellular domain. The association of this protein with SCARF1 is suppressed by the presence of scavenger ligands. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

SCARF2 links:

ENSG00000277971 (HGNC:):

ENSG00000277971 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-20429630-TCA-T is Pathogenic according to our data. Variant chr22-20429630-TCA-T is described in ClinVar as [Pathogenic]. Clinvar id is 31047.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARF2	NM_182895.5 link	c.1328_1329delTG	p.Val443AspfsTer78	frameshift_variant	Exon 8 of 11	ENST00000622235.5	NP_878315.2	Q96GP6-2
SCARF2	NM_153334.7 link	c.1328_1329delTG	p.Val443AspfsTer83	frameshift_variant	Exon 8 of 11		NP_699165.3	Q96GP6-1
SCARF2	XM_047441585.1 link	c.1442_1443delTG	p.Val481AspfsTer78	frameshift_variant	Exon 8 of 11		XP_047297541.1
SCARF2	XM_017029065.3 link	c.1328_1329delTG	p.Val443AspfsTer79	frameshift_variant	Exon 8 of 11		XP_016884554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCARF2	ENST00000622235.5 link	c.1328_1329delTG	p.Val443AspfsTer78	frameshift_variant	Exon 8 of 11	1	NM_182895.5	ENSP00000477564.2	Q96GP6-2
ENSG00000277971	ENST00000429594.1 link	n.237_238delTG		non_coding_transcript_exon_variant	Exon 4 of 5	5		ENSP00000392268.1	H7BZZ5
ENSG00000277971	ENST00000429594.1 link	n.237_238delTG		3_prime_UTR_variant	Exon 4 of 5	5		ENSP00000392268.1	H7BZZ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461524

Hom.:

AF XY:

0.00

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Van den Ende-Gupta syndrome

Pathogenic:1

Dec 01, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided

Pathogenic:1

Jan 12, 2022

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20887961, 21108395) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over